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Harkin, A,Connor, TJ,Walsh, A,St John, N,Kelly, JP
Serotonergic mediation of the antidepressant-like effects of nitric oxide synthase inhibitors
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antidepressant behaviour depression forced swimming test nitric oxide synthase serotonin FORCED SWIMMING TEST IN-VIVO RAT 7-NITROINDAZOLE MICE RELEASE MODEL HIPPOCAMPUS REBOXETINE BEHAVIOR
Recent studies indicate that nitric oxide (NO) synthase inhibitors have antidepressant-like potential in various animal models. In the present study the behavioural activity of the NO synthase inhibitors, N-G-nitro-L-arginine (L-NA) and 7-nitroindazole (7-NI), were assessed in a modified rat forced swimming test (FST). Both L-NA and 7-NI, dose dependently reduced immobility and increased swimming behaviour in the rat FST. This behavioural profile parallels the one previously shown with selective serotonin re-uptake inhibitors and serotonergic agonists. Thus, we examined the role of serotonin mediating the behavioural effects of L-NA and 7-NI in the rat FST. Depletion of endogenous serotonin using para-chlorophenylalanine (pCPA; 3 X 150 mg/kg, i.p.) completely blocked L-NA (20 mg/kg, i.p.) and 7-NI (20 mg/kg, i.p.)-induced reductions in immobility and increases in swimming behaviour during the FST. In conclusion these observations suggest that NO synthase inhibitors elicit their antidepressant-like activity in the modified swimming test through a serotonin dependent mechanism. (C) 2003 Elsevier Science Ltd. All rights reserved.
DOI 10.1016/S0028-3908(03)00030-3
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